SLC9A5 solute carrier family 9 member A5 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC9A5provided by HGNC
Official Full Name: solute carrier family 9 member A5provided by HGNC
Primary source: HGNC:HGNC:11078
See related: Ensembl:ENSG00000135740 MIM:600477; AllianceGenome:HGNC:11078
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: NHE5
Summary: Enables arrestin family protein binding activity and sodium:proton antiporter activity. Involved in regulation of intracellular pH and sodium ion transmembrane transport. Located in several cellular components, including focal adhesion; neuron spine; and recycling endosome membrane. Implicated in end stage renal disease. [provided by Alliance of Genome Resources, Jul 2025]
Expression: Biased expression in spleen (RPKM 6.3), testis (RPKM 2.2) and 7 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 16q22.1

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2025_08	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (67248979..67272191)
RS_2025_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (73043264..73066486)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (67282882..67306094)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

High NHE5 expression is associated with glioma.
Title: NHE5 regulates growth factor signaling, integrin trafficking, and degradation in glioma cells.
These data reveal a unique role for AMPK and NHE5 in regulating the pH homeostasis of hippocampal neurons during metabolic stress.
Title: Activation of AMP-activated protein kinase regulates hippocampal neuronal pH by recruiting Na(+)/H(+) exchanger NHE5 to the cell surface.
overexpression of NHE5 inhibits spine growth in response to neuronal activity
Title: Regulation of dendritic spine growth through activity-dependent recruitment of the brain-enriched Na⁺/H⁺ exchanger NHE5.
discrete elements of an elaborate sorting signal in NHE5 contribute to beta-arrestin2 binding and trafficking along the recycling endosomal pathway.
Title: CK2 phosphorylation of an acidic Ser/Thr di-isoleucine motif in the Na+/H+ exchanger NHE5 isoform promotes association with beta-arrestin2 and endocytosis.
SCAMP2 regulates NHE5 transit through recycling endosomes and promotes its surface targeting in an Arf6-dependent manner.
Title: Secretory Carrier Membrane Protein 2 Regulates Cell-surface Targeting of Brain-enriched Na+/H+ Exchanger NHE5.
observations demonstrate that NHE5 is localized to the recycling endosomal pathway and is dynamically regulated by phosphatidylinositol 3'-kinase and by the state of F-actin assembly
Title: Clathrin-mediated endocytosis and recycling of the neuron-specific Na+/H+ exchanger NHE5 isoform. Regulation by phosphatidylinositol 3'-kinase and the actin cytoskeleton.
beta-Arrestins bind and decrease cell-surface abundance of the Na+/H+ exchanger NHE5 isoform.
Title: beta-Arrestins bind and decrease cell-surface abundance of the Na+/H+ exchanger NHE5 isoform.
RACK1 activates NHE5 both by integrin-dependent and independent pathways, which may coordinate cellular ion homeostasis during cell-matrix adhesion.
Title: RACK1 associates with NHE5 in focal adhesions and positively regulates the transporter activity.

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Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Protein	Gene	Interaction	Pubs
Nef	nef	EIPA, a potent and specific inhibitor of Na+/H+ exchanger activity, significantly inhibits the Nef internalization into M2-macrophages, indicating that Nef is imported by Na+/H+ exchanger (solute carrier family 9, subfamily A)	PubMed

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D8S2279 (e-PCR)
- UniSTS:473907

D16S318 (e-PCR)
- UniSTS:148280

G44334 (e-PCR)
- UniSTS:95121

D16S421 (e-PCR), detects polymorphism
- UniSTS:8350

RH70396 (e-PCR)
- UniSTS:79025

GDB:591113 (e-PCR)
- UniSTS:157894

RH103456 (e-PCR)
- UniSTS:97781

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables antiporter activity	IEA Inferred from Electronic Annotation more info
enables arrestin family protein binding	IDA Inferred from Direct Assay more info	PubMed
enables potassium:proton antiporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sodium:proton antiporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables sodium:proton antiporter activity	IDA Inferred from Direct Assay more info	PubMed
enables sodium:proton antiporter activity	IEA Inferred from Electronic Annotation more info
enables sodium:proton antiporter activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in monoatomic cation transport	IEA Inferred from Electronic Annotation more info
involved_in monoatomic ion transport	IEA Inferred from Electronic Annotation more info
involved_in monoatomic ion transport	TAS Traceable Author Statement more info
involved_in potassium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in proton transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in regulation of intracellular pH	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of intracellular pH	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of pH	IEA Inferred from Electronic Annotation more info
involved_in sodium ion import across plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
involved_in sodium ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in sodium ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in sodium ion transport	IEA Inferred from Electronic Annotation more info
involved_in transmembrane transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in anchoring junction	IEA Inferred from Electronic Annotation more info
located_in cell projection	IEA Inferred from Electronic Annotation more info
located_in dendritic spine membrane	IEA Inferred from Electronic Annotation more info
located_in endosome	IEA Inferred from Electronic Annotation more info
located_in focal adhesion	IDA Inferred from Direct Assay more info	PubMed
located_in focal adhesion	IEA Inferred from Electronic Annotation more info
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in membrane	TAS Traceable Author Statement more info	PubMed
located_in neuron spine	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in postsynaptic membrane	IEA Inferred from Electronic Annotation more info
located_in recycling endosome membrane	IDA Inferred from Direct Assay more info	PubMed
located_in recycling endosome membrane	IEA Inferred from Electronic Annotation more info
located_in synapse	IDA Inferred from Direct Assay more info	PubMed
located_in synapse	IEA Inferred from Electronic Annotation more info
located_in synaptic membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: sodium/hydrogen exchanger 5

Names: NHE-5; Na(+)/H(+) exchanger 5; solute carrier family 9 (sodium/hydrogen exchanger), member 5; solute carrier family 9 member 5; solute carrier family 9, subfamily A (NHE5, cation proton antiporter 5), member 5

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001323971.2 → NP_001310900.1 sodium/hydrogen exchanger 5 isoform 2 precursor

Status: VALIDATED

Source sequence(s)

AC040160

Conserved Domains (1) summary

TIGR00840
Location:41 → 573

b_cpa1; sodium/hydrogen exchanger 3
NM_001323972.2 → NP_001310901.1 sodium/hydrogen exchanger 5 isoform 3 precursor

Status: VALIDATED

Source sequence(s)

AC040160

Related

ENSP00000598335.1, ENST00000928276.1
NM_001323973.2 → NP_001310902.1 sodium/hydrogen exchanger 5 isoform 4 precursor

Status: VALIDATED

Source sequence(s)

AC040160

Related

ENSP00000567551.1, ENST00000897492.1

Conserved Domains (2) summary

TIGR00840
Location:41 → 630

b_cpa1; sodium/hydrogen exchanger 3

pfam00999
Location:50 → 455

Na_H_Exchanger; Sodium/hydrogen exchanger family
NM_001323974.2 → NP_001310903.1 sodium/hydrogen exchanger 5 isoform 5

Status: VALIDATED

Source sequence(s)

AC040160
NM_001323975.2 → NP_001310904.1 sodium/hydrogen exchanger 5 isoform 6

Status: VALIDATED

Source sequence(s)

AC040160

Conserved Domains (2) summary

TIGR00840
Location:1 → 335

b_cpa1; sodium/hydrogen exchanger 3

cl01133
Location:1 → 160

Na_H_Exchanger; Sodium/hydrogen exchanger family
NM_004594.3 → NP_004585.1 sodium/hydrogen exchanger 5 isoform 1 precursor

See identical proteins and their annotated locations for NP_004585.1

Status: VALIDATED

Source sequence(s)

AF111173, AL137689, DB475730

Consensus CDS

CCDS42178.1

UniProtKB/Swiss-Prot

A5PKY7, Q14940, Q9Y626

Related

ENSP00000299798.11, ENST00000299798.16

Conserved Domains (1) summary

cl25615
Location:41 → 630

NhaP2; NhaP-type Na+/H+ and K+/H+ antiporter with C-terminal TrkAC and CorC domains [Energy production and conversion, Inorganic ion transport and metabolism]

RNA

NR_136664.2 RNA Sequence

Status: VALIDATED

Source sequence(s)

AC040160
NR_136665.2 RNA Sequence

Status: VALIDATED

Source sequence(s)

AC040160

Related

ENST00000564812.5
NR_136666.2 RNA Sequence

Status: VALIDATED

Source sequence(s)

AC040160
NR_136667.2 RNA Sequence

Status: VALIDATED

Source sequence(s)

AC040160